1. Field of the Invention
The present invention relates an apparatus and method of operating a chromatography column and, more particularly, to such a chromatography column and a method for effectively packing media and/or ensuring that the top flow adapter remains within a tolerance of being level and/or automatically moving the top flow adapter to at least one predetermined position.
2. Description of Related Art
Chromatography is a process of separating the components of a mixture of chemical substances through the percolation of fluid through a body or bed of comminuted or porous rigid material, known as media. In the process, the various component are often resolved, or separated, by their selective retardation as they are transported through the bed by a moving fluid or buffer. A solution of the substances to be separated becomes the moving phase of the system passing through the interstices in the stationary or continuous phase which are finely divided particles, possibly in the form of a gel slurry.
The substances in the moving phase are poured into the top of a chromatography column filled with the finely divided material, i.e., the media, that can absorb differentially the substances to be separated. The particular material used for the media varies widely with the substances to be separated. As the solution percolates down the column the components are separated from the buffer fluid which may be pumped back into the top of the column so as to again pass down through the bed as a carrier. The different substances as they travel down the column at different rates form bands of the different substances which are individually collected at the outlet.
A chromatography column typically comprises a hollow vertically disposed cylindrical housing including a liquid dispensing section, also referred to as a top flow adapter or plunger in many embodiments, at the upper end and through which the buffer and substances to be separated are dispensed to the media bed, and a liquid collecting section at the lower end for collecting the substances and buffer individually. The media or bed through which the buffer fluid and mixture to be separated and purified percolates is located between these sections. The liquid dispensing section and liquid collecting section may each include a respective distribution plate and at least one of the plates may be connected in an assembly with an axially movable plunger-like body positioned within the housing. After the column is charged with the bed media, the plunger body is often forced toward the bottom to compress or pressurize the media bed which has been poured into the column.
Prior art designs have allowed for the plunger to be moved with hydraulics manually controlled by an operator such as those shown and described in Applicant's U.S. Pat. No. 6,736,974, incorporated herein by reference. When the operator manually actuated the hydraulic controls of the prior art design, he or she would cause valves to open and shut to move the plunger up or down. There was no ability in this prior art design to have a controller move the plunger to a preset location. The operator had to attempt to stop at a preset location, which could be tricky. This is especially important during calibration steps. Also, there was no way to direct movement of one of the hydraulic cylinders independent of moving the other two in this prior art design.
The hydraulics in the prior art design provided a single hydraulic pressure from a control valve to each of three cylinders which moved the plunger. There was no way to ensure that each of the three cylinders moved in a manner to ensure that the top flow adapter moved in a level manner. If one side of the plunger became temporarily lodged on the inside of the column, or on pack material, it was easy for the plunger to become somewhat canted within the column. This is undesirable. The calculations performed by the pharmaceutical companies are often done with the assumption that the media pack is uniform. A lack of uniformity could adversely affect a run of product thereby causing unintended problems and a poor quality batch of pharmaceutical product.
The prior art packing technique involved an operator lowering a plunger until it stopped. If one of the cylinders encountered resistance, the other two could keep driving the plunger in a “canted” manner until they also stopped. A run of product could be performed with an unsatisfactory pack. This is believed to be undesirable.
Accordingly, a need exists to improve the operational methods by providing an improved chromatography column.